CN1695553A - Blood sugar level measuring apparatus - Google Patents

Abstract

PROBLEM TO BE SOLVED: To noninvasively measure a blood sugar level, based on temperature measurement.

Description

Blood-sugar level measuring device

Technical field

The nothing of measuring concentration of glucose in the organism that the present invention relates to need not take a blood sample is invaded blood-sugar level measuring method and device.

Background technology

People such as Hilson have reported behind diabetics intravenous injection glucose, the temperature below face and the tongue change (non-patent literature 1).People such as Scott have carried out discussing (non-patent literature 2) to diabetics and thermotaxic problem.According to these results of study, people such as Cho have proposed and need not take a blood sample, and obtain the method and the device (patent documentation 1,2) of concentration of glucose in the blood by measuring temperature.

In addition, calculate concentration of glucose for taking a blood sample and further carrying out various trials.For example, following method is proposed, near infrared light with 3 wavelength is measured the position, when detecting, detect body temperature through light intensity, obtain the representative value of 2 subdifferential values of absorptance, corresponding to the above-mentioned representative value of body temperature offset correction that predefined fiducial temperature produces, obtain the blood sugar concentration suitable (patent documentation 3) with revised representative value.Also provide,, measured the dim light degree, and measured the rely concentration of glucose device (patent documentation 4) of the reason that changes of the temperature that forms the dim light degree based on the rayed of variations in temperature moment while detect body temperature and carry out preheating or cooling measuring the position as lower device.Reported in addition as lower device, got, calculated the device (patent documentation 5) of concentration of glucose by 1 formula of logarithm of exporting and body temperature with reference to the output that sees through light behind light and the irradiation sample.

[non-patent literature 1] Diabete ﹠amp; Metabolisme, " Facial and sublingualtemperature changes following intravenous glucose injection in diabetics " by R.M.Hilson and T.D.R.Hockaday, 1982,8,15-19

[non-patent literature 2] Can.J.Physiol.Pharmacol., " Diabetes mellitus andthermoregulation ", by A.R.Scott, T.Bennett, I.A.MacDonald, 1987,65,1365-1376

The 5th, 924, No. 996 communiques of [patent documentation 1] United States Patent (USP)

The 5th, 795, No. 305 communiques of [patent documentation 2] United States Patent (USP)

[patent documentation 3] spy opens the 2000-258343 communique

[patent documentation 4] spy opens flat 10-33512 communique

[patent documentation 5] spy opens flat 10-108857 communique

Summary of the invention

Glucose in the blood (blood glucose) is used to produce and keep the necessary energy of organism in the intracellular glucose oxidase reaction.,, be to expect usually particularly so there is certain relation between concentration of glucose in the blood and the body temperature because the energy that produces is most of as the heat energy that is used to keep body temperature at the state of basal metabolism.But if consider the sick heating that causes, then obviously body temperature also can cause change by the principal element beyond the concentration of glucose in the blood.In the past, obtained the method for concentration of glucose in the blood by measuring temperature, had enough precision hardly although proposed to take a blood sample.

The purpose of this invention is to provide can be according to detected person's temperature data, method and the device that need not take a blood sample and obtain concentration of glucose in the blood accurately.

Blood glucose by vascular system particularly blood capillary offer the cell of whole body.Have complicated metabolic pathway in human body, glucose oxidase comes down to blood glucose and oxygen reaction, generates the reaction of water, carbon dioxide and energy.Here said oxygen is the oxygen by the blood supply cell, and the oxygen supply amount is by the hemoglobin concentration in the blood, hemoglobin saturation with oxygen and blood flow decision.On the other hand, the heat that is produced in vivo by glucose oxidase is seized by health by modes such as convection current, heat radiation, conduction.The inventor thinks that body temperature depends on the promptly living heat of energy growing amount of intravital glucose burning generation and the balance of heat radiation, and has conceived as drag:

(1) giving birth to heat and heat dissipation capacity is considered as equating.

(2) give birth to the function that heat is concentration of glucose and oxygen supply amount in the blood.

(3) the oxygen supply amount is determined by the blood flow in hemoglobin saturation with oxygen and the blood capillary in blood hemoglobin concentration, the blood.

(4) heat dissipation capacity is mainly by thermal convection current and heat radiation decision.

According to this model, find body surface is carried out heat determination, measure parameter relevant and the parameter relevant simultaneously with blood flow with oxygen concentration in the blood, adopt these measurement results can obtain blood glucose value accurately, thereby finished the present invention.One of as an example, can the part of human body for example finger tip carry out to obtaining the mensuration of above-mentioned parameter as determination object.The parameter relevant with convection current and radiation can be tried to achieve by finger tip is carried out heat determination.With the relevant parameter of hemoglobin saturation with oxygen in blood hemoglobin concentration and the blood, can measure hemoglobin in the blood in the spectroscopy mode, by in conjunction with the hemoglobin of oxygen with do not obtain in conjunction with the hemoglobin ratio of oxygen.In addition, for the parameter relevant,, adopt the constant of storage in advance also can too big infringement not arranged to measuring precision even particularly do not measure with blood hemoglobin concentration and hemoglobin saturation with oxygen.The parameter relevant with blood flow can be obtained from the hot transfer amount of skin by measuring.

Blood-sugar level measuring device of the present invention, as one of example, it has: measure a plurality of temperature from body surface, obtain being used to calculating and calorimetry portion from the information of relevant convection heat transfer' heat-transfer by convection amount of the heat radiation of above-mentioned body surface and radiant heat transfer amount, the oxygen that obtains the information relevant with oxygen amount in the blood measures the bonding part, the oxygen amount storage part of the relation of corresponding parameters and blood glucose value separately in storage and a plurality of temperature and the blood, to measure a plurality of measured values of importing the bonding part by calorimetry portion and oxygen and convert above-mentioned parameter separately to, and above-mentioned parameter is applicable to the above-mentioned relation that is stored in storage part and calculates the calculating part of blood glucose value and show the display part of the blood glucose value that calculates by calculating part.Oxygen measures the bonding part, has the blood flow determination portion that obtains the information relevant with blood flow and obtains the hemoglobin concentration in the blood, the optical detecting portion of hemoglobin saturation with oxygen.Blood flow determination portion, has the body surface contact site, be provided with in abutting connection with the body surface contact site in abutting connection with Temperature Detector, connect the body surface contact site and the heat-conduction component that is provided with and detect the heat-conduction component distance from the indirect temperature detector of body surface contact site more than or equal to the temperature of the position of 3.6mm.

Another example of blood-sugar level measuring device of the present invention, it has: the ambient temperature determinator of measuring ambient temperature, the body surface contact site of contact body surface, in abutting connection with the body surface contact site be provided with in abutting connection with Temperature Detector, mensuration is from the photothermal bolometric detectors of body surface, the heat-conduction component that connects the body surface contact site and be provided with, in abutting connection with heat-conduction component and be arranged on the indirect temperature detector that detects the temperature of the position of leaving the body surface contact site apart from the body surface contact site more than or equal to the position of 3.6mm, shine the light source of the light of at least 2 different wave lengths to the body surface contact site, detect the catoptrical photodetector that bright dipping produces in above-mentioned body surface reflection, having will be in abutting connection with Temperature Detector, the indirect temperature detector, the ambient temperature determinator, the output separately of bolometric detectors and photodetector converts the converter section of parameter respectively to, has the relation of storing above-mentioned parameter and blood glucose value in advance, and with above-mentioned parameter be applicable to above-mentioned relation calculate blood glucose value handling part calculating part and show display part by the blood glucose value of calculating part output.

Blood-sugar level measuring device of the present invention, as another example, it has: the ambient temperature determinator of measuring ambient temperature, the body surface contact site of contact body surface, be provided with in abutting connection with the body surface contact site in abutting connection with Temperature Detector, mensuration is from the photothermal bolometric detectors of body surface, the heat-conduction component that connects the body surface contact site and be provided with, in abutting connection with heat-conduction component and be arranged on apart from the position of body surface contact site more than or equal to 3.6mm, the indirect temperature detector of temperature of the position of body surface contact site is left in detection, the storage part of the information that storage is relevant with hemoglobin saturation with oxygen with the hemoglobin concentration in the blood, having will be in abutting connection with Temperature Detector, the indirect temperature detector, the output of ambient temperature determinator and bolometric detectors converts the converter section of a plurality of parameters to, has the relation of storing above-mentioned parameter and blood glucose value in advance, and with above-mentioned parameter be applicable to above-mentioned relation calculate blood glucose value handling part calculating part and show display part by the blood glucose value of calculating part output.

According to the present invention, can provide high-precision nothing to invade blood-sugar level measuring device and assay method.

Description of drawings

Fig. 1 is the illustraton of model that the heat of explanation from the body surface to the module shifts;

Fig. 2 is the expression temperature T ₁And temperature T ₂The figure that changes of time of measured value;

Fig. 3 represents temperature T ₃The mensuration example that changes of time;

Fig. 4 is the measured value of the various pick offs of diagram and the key diagram of relation of the parameter of derivation thus;

Fig. 5 is the figure of explanation size etc.;

Fig. 6 is the figure of the relation of expression skin temperature and blood flow;

Fig. 7 is the figure of the relation of explanation blood flow and skin heat conductivity;

Fig. 8 is the figure of explanation conduction of heat situation;

Fig. 9 is the figure that description time and temperature are soaked into the relation of thickness;

Figure 10 is the figure that the explanation temperature is soaked into the time rate of change of thickness;

Figure 11 is the vertical view that nothing of the present invention is invaded blood-sugar level measuring device;

Figure 12 is the figure of the operating procedure of indication device;

Figure 13 is the details drawing of determination part;

Figure 14 is the concept map that is illustrated in the flow chart of data processing in the device;

Figure 15 is the drafting figure of the glucose concentration determination value of concentration of glucose value of calculation of the present invention and enzyme electrode method;

Figure 16 is other routine details drawings of expression determination part;

Figure 17 is the concept map that is illustrated in the data storing place in the device;

Figure 18 is the drafting figure of the glucose concentration determination value of concentration of glucose value of calculation of the present invention and enzyme electrode method.

Description of reference numerals

11 ... operating portion, 12 ... determination part, 13 ... display part, 15 ... the finger placement section, 16 ... the opening of radiation temperature transducer portion, 17 ... contact temperature sensor portion, 18 ... optical pickocff portion, 21 ... metallic plate, 22 ... heat-conduction component, 23 ... critesistor, 24 ... critesistor, 25 ... infrared lenses, 26 ... the infrared ray penetrating window, 27 ... pyroelectric detector, 28 ... critesistor, 31,32 ... fiber optics, 33,34 ... light source, 35 ... photodiode

The specific embodiment

Below, with reference to accompanying drawing embodiments of the present invention are described.

At first, concrete aforementioned model is described.When considering the heat dissipation capacity problem, relevant with the temperature difference between the shell temperature as the convection heat transfer' heat-transfer by convection and the ambient temperature (room temperature) of its principal element.As the radiation-induced heat dissipation capacity of another principal element,, proportional with 4 powers of shell temperature according to Si Difen-boltzmann law.Thereby, know from the heat dissipation capacity of human body relevant with room temperature and shell temperature.On the other hand, can be expressed as the product of hemoglobin concentration, hemoglobin saturation with oxygen and blood flow as the oxygen supply amount of a principal element relevant with giving birth to heat.

Herein, hemoglobin concentration can be measured by the absorptance of the equal wavelength (waiting the extinction wavelength) of the molar absorption coefficient of HbO2 Oxyhemoglobin and reduction (deoxidation) hemoglobin.Hemoglobin saturation with oxygen can be by measuring, and the absorptance of the known another one at least of the ratio wavelength of the absorptance of above-mentioned wavelength such as extinction such as grade and the molar absorption coefficient of HbO2 Oxyhemoglobin and reduction (deoxidation) hemoglobin is found the solution simultaneous equations and measured.That is, hemoglobin concentration and hemoglobin saturation with oxygen can obtain by the absorptance of measuring minimum 2 wavelength.

Remaining is blood flow determination.Blood flow can be measured by the whole bag of tricks, and an example to its assay method describes below.

Fig. 1 illustrates when leaving the illustraton of model that the heat from the body surface to the piece shifts after having the solid modules contact body surface certain hour of certain degree thermal capacity.The module material can be with resins such as plastics, for example vinyl chloride.Be conceived to the temperature T of module and body surface contact portion herein, ₁Over time, reach the temperature T of leaving the position of body surface on module top ₂Over time.Blood flow can be mainly by following the trail of temperature T ₂The time of (temperature of the point that leaves the body surface certain space on module) changes infers.Explain below.

Module is with before body surface contacts, the temperature T of 2 points of module ₁, T ₂With room temperature T _rEquate.As shell temperature T _sThan room temperature T _rWhen high, if module contacts temperature T with body surface ₁Owing to shift and rising rapidly, and near shell temperature T from the heat of skin _sOn the other hand, owing to be transmitted to the interior heat of module from solid modules surface heat release, temperature T ₂Compare T ₁Decay, and stable the rising.Temperature T ₁, T ₂Depend on the hot transfer amount from the body surface to the module over time.Hot transfer amount from the body surface to the module depends on the blood flow in the blood capillary that flows through under the skin.If blood capillary is regarded as heat exchanger, the function that the heat transfer coefficient from blood capillary to cell tissue on every side can be used as blood flow is presented.Thereby, by following the trail of temperature T ₁, T ₂Over time, if measured the hot transfer amount from the body surface to the module, just can infer the amount of thermal conduction from the blood capillary to cell tissue, and can infer blood flow thus.Therefore, follow the trail of T by changing in time ₁, T ₂Variations in temperature, if measured the hot transfer amount from the body surface to the module, just can infer the amount of thermal conduction from the blood capillary to cell tissue, and can infer blood flow thus.

Fig. 2 is illustrated in the module and the temperature T of body surface contact portion ₁, and the temperature T of leaving the position on the module behind the body surface contact position ₂The time dependent figure of measured value.T when module contacts with body surface ₁Measured value rises rapidly, slowly descends during separation.

Fig. 3 represents the temperature T by radiation temperature detector mensuration ₃Measured value over time.Because as temperature T ₃Mensuration is from the radiating temperature of body surface, therefore than other sensor for temperature reacting condition sensitivities.Because radiant heat is with electromagnetic wave propagation, so can transmit variations in temperature in moment.Therefore, for example,, detect near the photothermal module of body surface and the body surface contact position if the radiation temperature detector is arranged on as following shown in Figure 13, just can be from temperature T ₃Change-detection go out module and body surface contact the t zero hour _StartAnd the contact t finish time _EndFor example, design temperature threshold value as shown in Figure 3 is set at the contact t zero hour in the time of will be above threshold value _Start, will when threshold value begins to descend, be set at the contact t finish time _EndTemperature threshold for example is set at 32 ℃ etc.

Then, by S type curve for example the mathematical logic curve make t constantly _StartWith moment t _EndBetween T ₁Measured value is approximate.The mathematical logic curve adopts temperature to be T, to represent for the following formula of t constantly.

[several 1]

$T=\frac{\mathrm{<figure-callout\; id="1"\; label="b"\; filenames="A20041009852300291.png"\; state="\{\{state\}\}">b</figure-callout>}}{1+c\&times;\exp (-a\&times;i)}+d$

Can try to achieve coefficient a by adopting nonlinear least square method, b, c, d and make measured value approximate.To the approximate expression of trying to achieve, T from moment t _StartTo moment t _EndPrincipal value of integral is as S ₁

Equally, by T ₂Measured value is calculated integrated value S ₂At this moment, (S ₁-S ₂) more little, mean from the finger surface to T ₂The hot transfer amount of position is big more.In addition, finger t time of contact _CONT(=t _End-t _Start) long more, (S ₁-S ₂) big more.Thus, a ₅As proportionality coefficient, a ₅/ (t _CONT* (S ₁-S ₂)) as the parameter X of representing blood flow ₅

Based on above explanation, for obtaining concentration of glucose in the blood, the variations in temperature of necessary measured quantity room temperature (ambient temperature), the module that shell temperature contacts with body surface, need know from the radiating temperature of body surface and the absorptance of minimum 2 wavelength etc. by aforementioned model.

Fig. 4 is the measured value of the various pick offs of diagram and the key diagram of relation of the parameter of derivation thus.The module that preparation contacts with body surface is by being provided with 2 kinds of temperature T of 2 temperature sensor measurements at its 2 place ₁And T ₂Over time.In addition, measure the radiation temperature T of body surface ₃With room temperature T ₄Measure the absorptance A of at least two kind wavelength relevant with the absorption of hemoglobin ₁, A ₂By temperature T ₁, T ₂, T ₃, T ₄Obtain the parameter relevant with blood flow.By temperature T ₃Obtain the parameter relevant, by temperature T with the radiant heat transfer amount ₃And temperature T ₄Obtain the parameter relevant with the convection heat transfer' heat-transfer by convection amount.In addition, by absorptance A ₁Obtain the parameter relevant, by absorptance A with hemoglobin concentration ₁And A ₂Obtain the parameter relevant with hemoglobin saturation with oxygen.

Fig. 5 is the skeleton diagram of the module used among the present invention.At this, the consideration diameter is that R, length are that the cylinder module of L is as module.Can know clearly that based on above-mentioned explanation the size (length L (m), diameter R (m)) of the module that is provided with for the size of inferring the blood flow shown in Fig. 1 and thermal characteristics be pyroconductivity λ (J/smK), thermal capacity U (J/K: specific heat capacity cv (J/Kkg) * block density ρ (kg/m for example ³) * module volume V (m ³)) be the key factor that precision is measured in decision.Herein, pyroconductivity λ is the inherent value of material of the material of composition module, the easy degree of expression control transfer of heat.And thermal capacity U represents to cause how the temperature of module changes owing to supply to the heat of module.And then measuring at what position x (m) of the contact point of spacing module and thermal source also is that thermal characteristics with above-mentioned module determines accuracy factors equally.

Fig. 6 represents the relation of the skin temperature of the blood flow pointed and finger.In addition, Fig. 7 represents the relation of the pyroconductivity of the blood flow of finger skin and finger skin.Shown in two figure, the blood flow of finger can be known by the pyroconductivity of measuring finger skin temperature or finger skin.Wherein, the pyroconductivity of DBF and finger skin is direct correlation.The finger skin temperature is by result's decision of pyroconductivity, finger interior temperature and the ambient temperature of the finger skin that determines by DBF.That is to say that because the internal temperature of terminal body of finger etc. is according to environmental change, even therefore the skin temperature of finger is identical, the temperature of finger interior also can be different and different blood flows arranged sometimes.Therefore, just must measure the pyroconductivity of finger skin for the correct blood flow of measuring finger skin.

When human body is in rest state, by giving birth to thermogenetic heat flow M (J/sm ²), the heat flow C (J/sm that dispels the heat by the conduction of heat of skin ²) and the heat flow R (J/sm that dispels the heat by radiation ²) satisfy relation of plane down, be in thermal equilibrium state.

M＝C+R

In fact also there is the heat radiation followed with the water evaporates that produces at body surface etc., ignores at this.

In addition, at the thermal equilibrium state that above-mentioned relation is set up, the conduction of heat from skin inside to skin surface is in normal conduction of heat state, satisfies relation of plane down.

M＝λ0((T0-Ts)/L)

Herein, λ 0 is the pyroconductivity of finger skin, and T0 is the internal temperature of finger, and Ts is the skin surface temperature of finger, and L is the skin thickness of finger.Usually the thickness of skin is certain, is assumed to known value at this.By measuring the heat flow C (J/sm that dispels the heat by the skin heat conduction ²) and the heat flow R (J/sm that dispels the heat by radiation ²) can know by giving birth to thermogenetic heat flow M.But, in fact in order to determine heat flow C (J/sm by heat conducting and radiating ²) necessary parameter is the coefficient of overall heat transmission h (J/sm of air ²K) difference is very big under air flow condition.Specifically, by free convection in air flow range near forced convertion, satisfy following formula:

1＜h(J/s·m ²·K)＜300

Thereby the heat flow that correct mensuration is dispelled the heat by conduction of heat is difficult.Therefore, as shown in Figure 1, measure by giving birth to thermogenetic heat flow M by the skin surface that makes module contact finger.

Then, illustrate by the example of contact modules mensuration by the assay method of giving birth to thermogenetic heat flow M.At this, the size of module and thermal characteristics unobvious heat conducting state of stablizing that destroys from skin inside to skin surface when making module contact finger surface.That is to say, need satisfy q M to the mobile heat flow q of the module that is contacted from the skin surface of pointing.In order to satisfy this condition, must satisfy relation of plane down.

When making object A contact another object B of certain temperature, the heat flow that the contact surface by two articles flows through is clipped in the interface and is saved.And, this heat flow, A can be used as in the short time of semo-infinite object processing at the contact object, was expressed as follows.

q＝λ1(Ts-Tr)/(παt)

At this, Ts is the surface temperature of object B, Tr be object A at ambient temperature the initial stage temperature and and the temperature of contact surface end opposite, λ 1 is the pyroconductivity of object A, α is the temperature conductivity of object A, t is the time.

Therefore, the condition of above-mentioned explanation is expressed as follows:

M=C+R=q=λ 1 (Ts-Tr)/ (π α t) in heat radiation from human body, the heat flow C (J/sm that dispels the heat by the conduction of heat of skin ²) amount and the heat flow R (J/sm that dispels the heat by radiation ²) amount roughly the same, be 20～30J/sm ²About.Thus, by making the conduction of heat that produces by the contact of module for by about the 2 times thermal characteristicss of coming regulation module of human body, roughly can satisfy the above-mentioned such condition of heat conducting state of stablizing that when making module contact finger surface, can obviously not destroy from skin inside to skin surface to the heat conducting amount of air.Therefore, to characteristic, pyroconductivity λ (J/smK), specific heat capacity cv (JKkg), the block density ρ (kg/m of module ³) regulation, be assumed to t (s) time of contact that employing will be measured usefulness, make therebetween the relation that equates by the heat that unit are shifted promptly

h·t＝2λ(t/π/α)

For example, when t=10s, obtain

3＜(λ·cv·ρ)＜900。Condition 1 (during minute 10s)

As satisfying condition 1 material, can enumerate resin the most general in the resin material, for example polrvinyl chloride and ABS resin (resin that constitutes by acrylonitrile (A), butadiene (B), styrene (S)).For the characteristic of ABS, general value is pyroconductivity λ=0.2 (J/smK), specific heat capacity cv=1600 (J/Kkg), block density ρ=1060 (kg/m ³).Thereby, for example during minute t=10s, obtain

 (λ cv ρ)=582, it satisfies condition 1.In addition, for the characteristic of polrvinyl chloride, general value is pyroconductivity λ=0.17 (J/smK), specific heat capacity cv=1640 (J/Kkg), block density ρ=1390 (kg/m ³).Thereby, for example during minute t=10s, obtain

 (λ cv ρ)=622 satisfies condition 1.Moreover 1 material is generally considered resin as satisfying condition.And preferred conductivity is the material to the 0.3J/smK about 0.1J/smK.

In addition, in the assay method of disclosed blood glucose value, make the skin surface of module contact finger and carry out 2 temperature measuring in the above.The problem of critical condition of asking heat by Temperature Distribution like this is as inverse problem and vague generalization.Approximate solution as this inverse problem generally adopts consistency profiles.Adopting consistency profiles, can be essential condition be used as the processing of semo-infinite object as the object of calculating object.It is that it is defined as temperature and soaks into thickness (δ (m)) in the Temperature Distribution scope that produces because of the conduction of heat in the short time that object can be used as the processing of semo-infinite object.That is to say, measuring point is set in the minute of regulation, then calculate separating of inverse problem, can obtain the critical condition of heat by obtaining its measured value if the temperature that enlarges is soaked into the point of arrival of thickness.Temperature is soaked into the distance that thickness generally is the point from contact surface to 1% the variations in temperature that its surface temperature takes place.Determination object is the situation of the present invention of human body because the temperature of contact portion is about 30 ℃, therefore with 1% suitable be about 0.3 ℃.This temperature is soaked into thickness can be by following the providing of the heat conducting strict solution of instability.

δ＝3.6((t·λ)/(cv·ρ))

The ideograph that Temperature Distribution after Fig. 8 represents to make module and thermal source contacts changes.Along with the time changes, Temperature Distribution enlarges gradually from contact position, and final whole module produces Temperature Distribution.For the distribution of the moment t1 among the figure, temperature is soaked into thickness and is compared very short with block length.Be not subjected to the influence of the length of module in this state Temperature Distribution, module can be handled as the semo-infinite object.In addition, even at moment t2, temperature is soaked into thickness and is compared still very shortly with block length, and therefore, Temperature Distribution is not subjected to the influence of the length of module, can consider module can be handled as the semo-infinite object.But, at moment t3 since temperature to soak into thickness long than block length, so Temperature Distribution becomes the shape of the effect length that is subjected to module.In this situation, use the assay method of module to be false.Thereby, in the assay method that uses module, must use to have the module of soaking into the length of thickness more than or equal to temperature.

As mentioned above, temperature is soaked into rerum natura and and the time of contact (minute) of thermal source that thickness depends on module.Therefore, if determined to form the material of module, then will be prescribed as the time of the mensuration establishment of module and the necessary length of module with this material.The relation that minute t when Fig. 9 represents with polrvinyl chloride and ABS resin as material and temperature are soaked into thickness δ.In Fig. 9, when having represented use polrvinyl chloride and ABS resin, in minute t, set up the relation of the block length L of necessary minimum for the mensuration that adopts module.

In addition, Figure 10 is the time rate of change that the temperature represented among Fig. 9 is soaked into thickness, is to depend on temperature conductivity (m ²/ s) value.

Known to this figure, minute during smaller or equal to 10s temperature to soak into the time rate of change of thickness big, show that temperature takes place sharply to change.In contrast, if minute more than or equal to 10s, it is roughly certain that temperature is soaked into the time rate of change of thickness.This influence that shows the deviation (this is because the detected person confirms the signal that determinator sends, and makes the such mensuration process of action thereupon) of minute is that boundary can great changes will take place with minute 10s.Thereby, as Figure 10, shown in Figure 9, because the T2 temperature measuring error that the deviation of said determination time produces can define big scope and little scope.Like this, for suppressing mensuration precision deterioration, preferably make minute more than or equal to 10s by the deviation generation of minute.

As mentioned above, show owing to measure the requirement of precision aspect to be preferably greater than the minute that equals 10s, thereby in order to obtain high-precision measurement result and the minimum length of regulation module by the mensuration of using module.By Fig. 9, the saturating thickness of hot dipping the when minimum length of this module can be used as minute (with the time of contact of thermal source) for 10s obtains.Thereby the length L of module must satisfy following condition 2.

L '＞δ condition 2

In addition, for measuring point x, in the formula of the saturating thickness of above-mentioned hot dipping, be arranged on and can soak into thickness distance about equally in the hope of temperature from contact point at the point of having stipulated to measure behind the minute module temperature.Thereby the x that locates must satisfy following condition 3.

X＞δ condition 3

Condition 2,3 should satisfy above-mentioned condition 1 simultaneously.Making the minute lower limit is 10s, for the value of condition 1, be to use rerum natura (pyroconductivity λ=0.2 (J/smK), specific heat capacity cv=1600 (J/Kkg), the block density ρ=1060 (kg/m of ABS resin ³)), then temperature is soaked into thickness (δ (m)) and is about 3.6mm.Also value under the situation of polrvinyl chloride with degree.That is to say that the condition (condition 2) of obtaining the length L of module is

L＞3.6mm, in addition, the condition (condition 3) of obtaining measuring point for the temperature is

x＞3.6mm。

By above explanation, stipulated that measuring principle is to the thermal characteristics of contact modules requirement and length and then stipulated the temperature measuring position.In addition, the contact area of module and finger has also been done same regulation.The contact area of this module and finger is equivalent to the sectional area of module.The most basic requirement of regulation module sectional area is the size of finger.Because the size (width) of finger is about 10mm to 15mm, so as the condition that the frequent repeatability of described finger is contacted well, the diameter (R (m)) that requires the contact portion of module is smaller or equal to 1/2 of the width of finger.

Thereby the diameter of the contact portion of module must satisfy following conditions (condition 4).

R＜7.5mm condition 4

Use is with the module in the scope of above-mentioned condition regulation and make module contact skin, measures variations in temperature at 2, can calculate the heat flow qx that flows through module in fact gradually by separating inverse problem.Obtain the relation of following formula by this mensuration.

M＝λ0((T0-Ts)/L)＝qx

By with described value with contain module as concentrating thermal capacity to consider and the λ 0 that obtains during with circuit simulation model and the formula of T0 are found the solution the pyroconductivity λ 0 that calculates the skin that should try to achieve as simultaneous equations.Use relation shown in Figure 7 can obtain the information relevant by described value with blood flow.

Then, describe realizing the concrete apparatus structure that does not have the intrusion blood glucose value according to principle of the present invention.

Figure 11 is the vertical view that nothing of the present invention is invaded blood-sugar level measuring device.Use the skin of finger tip tripe in this device as body surface, also can use other body surface.

On device, be provided with operating portion 11, place the determination part 12 of determination object finger, show the display part 13 of measurement result, unit state and measured value etc.In operating portion 11, dispose promising 4 button 11a～11d that carry out the device operation.In determination part 12, be provided with and cover 14, open when covering 14 (states that the figure expression is uncapped), there is finger placement section 15 with oval circumference.In finger placement section 15, opening 16, contact temperature sensor portion 17 and the optical pickocff portion 18 of radiation temperature transducer portion arranged.

The operating procedure of Figure 12 indication device.If press the button engaging means power supply of operating portion, show on liquid crystal display then " preheating " that the electronic circuit in the device is preheated.Simultaneously, trace routine running, detected electrons circuit automatically.If " preheating " finishes, then show " please place finger " at liquid crystal display part.If finger is placed on the finger placement section, show countdown at liquid crystal display part.When countdown finishes, show " please remove finger " at liquid crystal display part.If finger is left the finger placement section, then show " in the date processing " at liquid crystal display part.Then, show blood glucose value at liquid crystal display part.At this moment, the blood glucose value of demonstration was stored in the IC-card (surface-mounted integrated circuit) together with the time on date.If the blood glucose value of reading displayed is pressed the button of operating portion.Device entered the state of waiting for mensuration next time, showing " please place finger " at liquid crystal display part after about 1 minute.

Figure 13 is the expression determination part figure of example in detail, (a) is vertical view, (b) is its XX sectional view, (c) is its YY sectional view.

At first, the temperature measuring to nothing intrusion blood-sugar level measuring device of the present invention describes.Part in detected portion (finger tip tripe) contact is provided with the metal sheet 21 that the high material of pyroconductivity is for example made of gold, be thermally connected to the low material of ratio metallic plate 21 pyroconductivities on this metallic plate 21, for example reach device inside by the bar-shaped heat-conduction component 22 that polrvinyl chloride constitutes.As temperature sensor, be provided with as the temperature of measuring metallic plate 21, to the critesistor 23 of the Temperature Detector of detected portion adjacency, and the critesistor 24 of the Temperature Detector that connects indirectly as the temperature of measuring the heat-conduction component part of only leaving metallic plate 21 certain distances, to detected portion.Be provided with infrared lenses 25 at the device interior location that can understand thoroughly the detected portion (finger tip tripe) that is placed on finger placement section 15, below infrared lenses 25, be provided with pyroelectric detector 27 via infrared ray penetrating window 26.In addition, be provided with another critesistor 28 near pyroelectric detector 27.

Heat-conduction component is as long as use the material of pyroconductivity in the scope of 0.1J/smK～0.3J/smK.In described example, use the ABS resin of pyroconductivity as 0.2J/smK as heat-conduction component.Also can use polrvinyl chloride to replace ABS resin.The shape of heat-conduction component can be that length is 7.5mm more than or equal to 3.6mm, diameter.In described example, making diameter is that 2mm, length are the cylindrical of 8mm.In addition, as long as critesistor 24 detects apart from the temperature of metallic plate 21 more than or equal to the position of 3.6mm.In described example, for the temperature of only measuring apart from the part of the heat-conduction component of metallic plate 5mm is provided with critesistor 24.

The temperature sensor portion of determination part has 4 temperature sensors like this, 4 kinds of temperature below measuring.

(1) temperature of finger surface (critesistor 23): T ₁

(2) temperature of heat-conduction component (critesistor 24): T ₂

(3) Shou Zhi radiation temperature (pyroelectric detector 27): T ₃

(4) room temperature (critesistor 28): T ₄

Then, optical pickocff portion 18 is described.Optical pickocff portion is hemoglobin concentration and a hemoglobin saturation with oxygen of obtaining necessity that the oxygen supply amount uses in order to measure.Measure hemoglobin concentration and hemoglobin saturation with oxygen, need to measure minimum 2 wavelength absorptance down, Figure 13 (c) expression is carried out 2 used configuration example of wavelength mensuration by 2 light sources 33,34 and 1 detector 35.

The end of 2 fiber optics 31,32 is arranged in optical pickocff portion 18.Fiber optics 31 is fiber optics that rayed is used, and fiber optics 32 is to accept the fiber optics that light is used.Shown in Figure 13 (c), fiber optics 31 and the ramose fiber 31a of formation, 31b links to each other, and is provided with the light emitting diode 33,34 of 2 wavelength at its end.Be provided with photodiode 35 at the end of accepting the fiber optics 32 that light uses.Light emitting diode 33 is launched the light of wavelength 810nm, and light emitting diode 34 is launched the light of wavelength 950nm.Wavelength 810nm is the mutually isochronous extinction wavelength that waits of HbO2 Oxyhemoglobin and the molar absorption coefficient of reduction (deoxidation) hemoglobin, and wavelength 950nm is the wavelength of the difference of molar absorption coefficient of HbO2 Oxyhemoglobin and reduced hemoglobin when big.

2 light emitting diode 33,34 timesharing ground are luminous, and the light that is sent by light emitting diode 33,34 shines on detected person's the finger with fiber optics 31 by rayed.Shine the light of finger,, inject and accept light with detected in the fiber optics 32 by photodiode 35 by the skin reflex of finger.During the skin reflex of the light that shines finger by finger, a part of light transmission skin is invaded organization internal, is absorbed by the hemoglobin in the blood that flows through blood capillary.The determination data of photodiode 35 is reflectance R, and absorptance is calculated approx with log (1/R).Light by wavelength 810nm and wavelength 950nm shines separately, measures the R value separately, and obtains log (1/R), measures the absorptance A of wavelength 810nm thus ₁Absorptance A with wavelength 950nm ₂

Suppose that reduced hemoglobin concentration is [Hb], HbO2 Oxyhemoglobin concentration is [HbO ₂], represent absorptance A with following formula ₁With absorptance A ₂

[several 2]

A ₁＝a×([Hb]×A _Hb(810nm)+[HbO ₂]×4H _bO2(810nm))

＝a×([Hb]+[HbO ₂])×A _HbO2(810nm)

A ₂＝a×([Hb]×A _Hb(950nm)+[HbO ₂]×A _HbO2(950nm))

$=a\&times;\left(\right[\mathrm{Hb}]+[\mathrm{Hb}{O}_2\left]\right)\&times;(I-\frac{\left[\mathrm{Hb}{O}_2\right]}{\left[\mathrm{Hb}\right]+\left[\mathrm{Hb}{O}_2\right]}\&times;A_{\mathrm{Hb}}\left(950\mathrm{nm}\right)+\frac{\left[\mathrm{Hb}{O}_2\right]}{\left[\mathrm{Hb}\right]+\left[\mathrm{Hb}{O}_2\right]}\&times;A_{\mathrm{Hb}{O}_2}\left(950\mathrm{nm}\right))$

A _Hb(810nm) and A _Hb(950nm), A _HbO2(810nm) and A _HbO2(950nm) being respectively the molar absorption coefficient of reduced hemoglobin, HbO2 Oxyhemoglobin, is known under each wavelength.A is a proportionality coefficient.Can obtain hemoglobin concentration ([Hb]+[HbO from following formula ₂]), hemoglobin saturation with oxygen { [HbO ₂]/[Hb]+[HbO ₂] as follows.

[several 3]

$\left[\mathrm{Hb}\right]+\left[\mathrm{Hb}{O}_2\right]=\frac{A_1}{a\&times;A_{\mathrm{Hb}{O}_2}\left(810\mathrm{nm}\right)}$

$\frac{\left[\mathrm{Hb}{O}_2\right]}{\left[\mathrm{Hb}\right]+\left[\mathrm{Hb}{O}_2\right]}=\frac{A_2\&times;A_{\mathrm{Hb}{O}_2}\left(810\mathrm{nm}\right)-{\mathrm{<figure-callout\; id="1"\; label="A"\; filenames="A20041009852300291.png"\; state="\{\{state\}\}">A</figure-callout>}}_1\&times;A_{\mathrm{Hb}}\left(950\right))}{A_1\&times;(A_{\mathrm{Hb}{O}_2}\left(950\mathrm{nm}\right)-A_{\mathrm{Hb}}\left(950\mathrm{nm}\right))}$

In addition, it is bright that the mensuration that describes the absorptance by 2 wavelength herein in detail is measured the example of hemoglobin concentration and hemoglobin saturation with oxygen, but also can pass through with 3 or its above wavelength mensuration absorptance, and the influence of reduction hindering factor improves and measures precision.

Figure 14 is the concept map of the flow chart of data processing in the indication device.In the device of this example, there are 5 pick offs forming by critesistor 23, critesistor 24, pyroelectric detector 27, critesistor 28 and photodiode 35.Owing to measure the absorptance of wavelength 810nm and the absorptance of wavelength 950nm, in device, import 6 kinds of measured values by photodiode 35.

5 kinds of analogue signals are passed through the amplifier of A1～A5 separately, and the analog-digital converter by AD1～AD5 carries out digital translation.By the value calculating parameter x after the digital translation _i(i=1,2,3,4,5).X particularly _iBe expressed as follows (a ₁～a ₅Be proportionality coefficient).

[several 4]

With the proportional parameter of heat radiation

x ₁＝a ₁×(T ₃) ⁴

With the proportional parameter of thermal convection current

x ₂＝a ₂×(T ₄-T ₃)

With the proportional parameter of hemoglobin concentration

$x_3=a_3\&times;\left(\frac{A_1}{a\&times;A_{\mathrm{Hb}{O}_2}\left(810\mathrm{nm}\right)}\right)$

With the proportional parameter of hemoglobin saturation with oxygen

$x_4=a_4\&times;\left(\frac{A_2\&times;A_{\mathrm{Hb}{O}_2}\left(810\mathrm{nm}\right)-{\mathrm{<figure-callout\; id="1"\; label="A"\; filenames="A20041009852300291.png"\; state="\{\{state\}\}">A</figure-callout>}}_1\&times;A_{\mathrm{Hb}}\left(950\right))}{A_1\&times;(A_{\mathrm{Hb}{O}_2}\left(950\mathrm{nm}\right)-A_{\mathrm{Hb}}\left(950\mathrm{nm}\right))}\right)$

With the proportional parameter of blood flow

$x_5=a_5\&times;\left(\frac{1}{t_{\mathrm{CONT}}\&times;(S_1-S_2)}\right)$

Then, the parameter x that obtains according to data by most healthy persons of reality and diabetics _iMeansigma methods and standard deviation calculation go out normalizing parameter.By following formula by each parameter x _iThe normalized parameter X _i(i=1,2,3,4,5).

[several 5]

$X_i=\frac{x_i-{\stackrel{\&OverBar;}{x}}_i}{\mathrm{SD}\left(x_i\right)}$

x _i: parameter

x _i: the meansigma methods of parameter

SD (X _i): the standard deviation of parameter

Get aforesaid 5 normalizing parameters, carry out conversion Calculation for the final concentration of glucose that shows.Necessary programs is stored among the ROM in handling calculating, and this ROM is built in the microprocessor that is contained in the device.In addition, necessary memory block is similarly guaranteed by the RAM that is installed in the device in handling calculating.The result of computing is presented on the liquid crystal display.

Necessary programs element when having deposited in as processing calculating in ROM is especially for the function of obtaining concentration of glucose C.This function definition is as follows.At first, C represents with following formula (1).a _i(i=0,1,2,3,4,5) are in advance by a plurality of determination data decisions.Ask a _iStep as follows.

(1) the multiple regression formula of the relation of formation expression normalizing parameter and concentration of glucose C.

(2) obtain the normal equation (simultaneous equations) of related normalizing parameter by the formula that obtains by method of least square.

(3) obtain coefficient a by normal equation _iThe value of (i=0,1,2,3,4,5) is in the substitution multiple regression formula.

At first, form expression concentration of glucose C and normalizing parameter X ₁, X ₂, X ₃, X ₄, X ₅The following regression equation (1) of relation.

[several 6]

C＝f(X ₁，X ₂，X ₃，X ₄，X ₅)

＝a ₀+a ₁X ₁+a ₂X ₂+a ₃X ₃+a ₄X ₄+a ₅X ₅……(1)

Then, in order to make the glucose concentration value C with the enzyme electrode method _iThe error minimum find the solution the multiple regression formula, adopt method of least square.The quadratic sum of supposing residual error is D, and then D represents with following formula (2).

[several 7]

$D=\underset{i=1}{\overset{n}{\mathrm{\&Sigma;}}}{d_i}^2$

$=\underset{i=1}{\overset{n}{\mathrm{\&Sigma;}}}{(C_i-f({\mathrm{<figure-callout\; id="1"\; label="X\; i"\; filenames="A20041009852300291.png"\; state="\{\{state\}\}">X</figure-callout>}}_i,X_{i2},X_{i3},X_{i4},X_{i5}))}^2$

$=\underset{i=1}{\overset{n}{\mathrm{\&Sigma;}}}{\{C_i-(a_0+a_1{\mathrm{<figure-callout\; id="1"\; label="X\; i"\; filenames="A20041009852300291.png"\; state="\{\{state\}\}">X</figure-callout>}}_i+a_2{X}_{i2}+a_3{X}_{i3}+a_4{X}_{i4}+a_5{X}_{i5})\}}^2\&CenterDot;\&CenterDot;\&CenterDot;\left(2\right)$

Residual sum of squares (RSS) D minimum is at a ₀, a ₁..., a ₅Formula (2) when partial differential equals zero, is obtained following formula thus.

[several 8]

$\frac{\&PartialD;D}{\&PartialD;a_0}=-2\underset{i=1}{\overset{n}{\mathrm{\&Sigma;}}}\{C_i-(a_0+a_1{\mathrm{<figure-callout\; id="1"\; label="X\; i"\; filenames="A20041009852300291.png"\; state="\{\{state\}\}">X</figure-callout>}}_i+a_2{X}_{i2}+a_3{X}_{i3}+a_4{X}_{i4}+a_5{X}_{i5})\}=0$

$\frac{\&PartialD;D}{\&PartialD;a_1}=-2\underset{i=1}{\overset{n}{\mathrm{\&Sigma;}}}{X}_{i1}\{C_i-(a_0+a_1{\mathrm{<figure-callout\; id="1"\; label="X\; i"\; filenames="A20041009852300291.png"\; state="\{\{state\}\}">X</figure-callout>}}_i+a_2{X}_{i2}+a_3{X}_{i3}+a_4{X}_{i4}+a_5{X}_{i5})\}=0$

$\frac{\&PartialD;D}{\&PartialD;a_2}=-2\underset{i=1}{\overset{n}{\mathrm{\&Sigma;}}}{X}_{i2}\{C_i-(a_0+a_1{\mathrm{<figure-callout\; id="1"\; label="X\; i"\; filenames="A20041009852300291.png"\; state="\{\{state\}\}">X</figure-callout>}}_i+a_2{X}_{i2}+a_3{X}_{i3}+a_4{X}_{i4}+a_5{X}_{i5})\}=0$

$\frac{\&PartialD;D}{\&PartialD;a_3}=-2\underset{i=1}{\overset{n}{\mathrm{\&Sigma;}}}{X}_{i3}\{C_i-(a_0+a_1{\mathrm{<figure-callout\; id="1"\; label="X\; i"\; filenames="A20041009852300291.png"\; state="\{\{state\}\}">X</figure-callout>}}_i+a_2{X}_{i2}+a_3{X}_{i3}+a_4{X}_{i4}+a_5{X}_{i5})\}=0$

$\frac{\&PartialD;D}{\&PartialD;a_4}=-2\underset{i=1}{\overset{n}{\mathrm{\&Sigma;}}}{X}_{i4}\{C_i-(a_0+a_1{\mathrm{<figure-callout\; id="1"\; label="X\; i"\; filenames="A20041009852300291.png"\; state="\{\{state\}\}">X</figure-callout>}}_i+a_2{X}_{i2}+a_3{X}_{i3}+a_4{X}_{i4}+a_5{X}_{i5})\}=0$

$\frac{\&PartialD;D}{\&PartialD;a_5}=-2\underset{i=1}{\overset{n}{\mathrm{\&Sigma;}}}{X}_{i5}\{C_i-(a_0+a_1{\mathrm{<figure-callout\; id="1"\; label="X\; i"\; filenames="A20041009852300291.png"\; state="\{\{state\}\}">X</figure-callout>}}_i+a_2{X}_{i2}+a_3{X}_{i3}+a_4{X}_{i4}+a_5{X}_{i5})\}=0\&CenterDot;\&CenterDot;\&CenterDot;\left(3\right)$

Suppose C, X ₁～X ₅The meansigma methods C that respectively does for oneself _Mean, X _1mean～X _5meanThe time, X _Imean=0 (i=1～5) obtain formula (4) according to formula (1) thus.

[several 9]

a ₀＝C _mean-a ₁X _1mean-a ₂X _2mean-a ₃X _3mean-a ₄X _4mean-a ₅X _5mean

＝C _mean ……(4)

In addition, the change co-variation between the normalizing parameter is with formula (5) expression, normalizing parameter X _iThe co-variation of (i=1～5) and C is with formula (6) expression.

[several 10]

$S_{\mathrm{ij}}=\underset{k=1}{\overset{n}{\mathrm{\&Sigma;}}}(X_{\mathrm{ki}}-X_{\mathrm{imean}})(X_{\mathrm{kj}}-X_{\mathrm{jmean}})=\underset{k=1}{\overset{n}{\mathrm{\&Sigma;}}}{X}_{\mathrm{ki}}{X}_{\mathrm{kj}}(i,j=\mathrm{1,2},..5)\&CenterDot;\&CenterDot;\&CenterDot;\left(5\right)$ (normal equation $S_{\mathrm{iC}}=\underset{k=1}{\overset{n}{\mathrm{\&Sigma;}}}(X_{\mathrm{ki}}-X_{\mathrm{imean}})(C_k-C_{\mathrm{mean}})=\underset{k=1}{\overset{n}{\mathrm{\&Sigma;}}}{X}_{\mathrm{ki}}(C_k-C_{\mathrm{mean}})(i,j=\mathrm{1,2},..5)\&CenterDot;\&CenterDot;\&CenterDot;\left(6\right)$

Wushu (4) (5) (6) substitution formula (3) is put in order, obtains simultaneous equations (normal equation) (7), obtains a by separating this equation ₁～a ₅

[several 11]

a ₁S ₁₁+a ₂S ₁₂+a ₃S ₁₃+a ₄S ₁₄+a ₅S ₁₅＝S _1C

a ₁S ₂₁+a ₂S ₂₂+a ₃S ₂₃+a ₄S ₂₄+a ₅S ₂₅＝S _2C

a ₁S ₃₁+a ₂S ₃₂+a ₃S ₃₃+a ₄S ₃₄+a ₅S ₃₅＝S _3C

a ₁S ₄₁+a ₂S ₄₂+a ₃S ₄₃+a ₄S ₄₄+a ₅S ₄₅＝S _4C

a ₁S ₅₁+a ₂S ₅₂+a ₃S ₅₃+a ₄S ₅₄+a ₅S ₅₅＝S _5C?……(7)

Obtain constant term a with formula (4) ₀The a that more than tries to achieve _i(i=0,1,2,3,4,5) are stored among the ROM when manufacturing installation.Do in actual the mensuration at use device, by the normalizing parameter X that obtains by measured value ₁～X ₅In the substitution regression equation (1), calculate concentration of glucose C.

Provide the object lesson of concentration of glucose computational process below.By the coefficient of a plurality of data of healthy person and diabetics mensuration being determined regression equation (1), the calculating formula of following concentration of glucose is stored among the ROM of microprocessor in advance.

[several 12]

C＝99.4+18.3×X ₁-20.2×X ₂-23.7×X ₃-22.0×X ₄-25.9×X ₅

X ₁～X ₅Be to parameter x ₁～x ₅Parameter after the standardization.Suppose that parameter distributions is a standard profile, then 95% value of getting from-2 to+2 of normalizing parameter.

With the measured value of healthy person as an example, normalizing parameter X ₁=-0.06, X ₂=+0.04, X ₃=+0.05, X ₄=-0.12, X ₅In the above-mentioned formula of=+ 0.10 substitution, obtain C=96mg/dl.In addition, with the measured value of diabetics as an example, normalizing parameter X ₁=+1.15, X ₂=-1.02, X ₃=-0.83, X ₄=-0.91, X ₅In the above-mentioned formula of=-1.24 substitutions, obtain C=213mg/dl.

Assay method in the past is in the enzyme electrode method, makes the blood and the reagent reacting that obtain by blood sampling, measures the electric weight that is produced by this reaction, measures blood glucose value.Below the measurement result of enzyme electrode method and the measurement result of one embodiment of the present of invention are stated.Measured value with healthy person is an example, when the concentration of glucose of enzyme electrode method is 89mg/dl, measuring the normalizing parameter X that obtains by the inventive method with the moment ₁=-0.06, X ₂=+0.04, X ₃=+0.05, X ₄=-0.12, X ₅In the above-mentioned formula of=+ 0.10 substitution, obtain C=96mg/dl.In addition, with the measured value of diabetics as an example, when the concentration of glucose of enzyme electrode method is 238mg/dl, with measuring the normalizing parameter X that obtains by the inventive method constantly ₁=+1.15, X ₂=-1.02, X ₃=-0.83, X ₄=-0.91, X ₅In the above-mentioned formula of=-1.24 substitutions, obtain C=213mg/dl.By above-mentioned result, can obtain concentration of glucose accurately by the inventive method and be confirmed.

Figure 15 is to be that value of calculation, the transverse axis of the concentration of glucose of the inventive method is the measured value of the concentration of glucose of enzyme electrode method with the longitudinal axis, is depicted as the figure of measured value separately at a plurality of patients.Can obtain good dependency (correlation coefficient=0.9324) by measure oxygen supply amount blood flow according to the inventive method.

In the above-described embodiment, relevant with hemoglobin saturation with oxygen in blood hemoglobin concentration and blood parameter is to try to achieve by the hemoglobin of measuring in the blood in the spectroscopy mode.; because hemoglobin concentration is stable for the people of symptoms such as no anemia, hemorrhage and erythrocyte increase disease; and; hemoglobin concentration is that 13～18g/dL, women are that 12～17g/dL is a normal value for the male; the amplitude of variation scope of hemoglobin concentration normal value is 5～6%; other are little for the weighted ratio of relevant with blood flow item in above-mentioned blood glucose value calculating formula, therefore, damage precision even handle as constant also not too largely.Equally, about hemoglobin saturation with oxygen, if under atmospheric pressure breathe air, be in peace and quiet, easily under the state, it is stabilized in 97～98%, therefore, also can be used as constant and handles.Thereby hemoglobin concentration and hemoglobin saturation with oxygen can be used as constant and handle, and the oxygen supply amount can be obtained by the long-pending of hemoglobin concentration constant, hemoglobin saturation with oxygen constant and blood flow.

Handle by hemoglobin concentration and hemoglobin saturation with oxygen being can be used as constant,, can remove optical pickocff etc. and simplified for the sensor construction that is used for blood-sugar level measuring.In addition, by the time of omission optical detecting and the time of optical detecting result treatment, can realize a series of rapid of blood-sugar level measuring.

In addition, because hemoglobin saturation with oxygen is stable value when particularly quiet, if therefore hemoglobin concentration and hemoglobin saturation with oxygen are handled as constant, then particularly the mensuration precision can be improved in the blood-sugar level measuring when peace and quiet, and a series of rapid of blood-sugar level measuring can be realized.At this, be meant when so-called quiet because of on being sitting in chair or when the recumbency health makes the active hardly state of health pass through about 5 minutes.

Below, the embodiment that hemoglobin concentration and hemoglobin saturation with oxygen are handled as constant is described.Present embodiment because identical with the foregoing description, at this, mainly describes the place different with the foregoing description except hemoglobin concentration and hemoglobin saturation with oxygen are handled as constant.

Present embodiment is not measured hemoglobin concentration and hemoglobin saturation with oxygen in Fig. 4 key diagram, and handles as constant.Thereby the determination part of present embodiment is made the structure of removing light source 33,34, photodiode 35 and fiber optics 31,32 from the determination part of the foregoing description shown in Figure 13 as shown in figure 16.The material of heat-conduction component 22, size and critesistor 24 and heat-conduction component 22 position contacting are same as the previously described embodiments.The parameter of Shi Yonging is and the proportional parameter x of heat radiation in the present embodiment ₁, with the proportional parameter x of thermal convection current ₂And and the proportional parameter x of oxygen supply amount ₃(below, with the proportional parametric representation of oxygen supply amount be x ₃), calculate normalizing parameter by these parameters such as above-mentioned processing, according to these 3 normalizing parameter X _i(i=1,2,3) calculate concentration of glucose.In date processing, can omit " by the conversion process of optics instrumentation amount data " (with reference to Figure 14) essential in the foregoing description to normalizing parameter.

Figure 17 is the functional block diagram of expression present embodiment device.This device is driven by battery 41.The signal of measuring by the sensor part that is made of temperature sensor 43 enters that (analog-digital converter AD1～AD4) converts digital signal to the corresponding analog-digital converter 44 that is provided with of each signal.As the peripheral circuit of microprocessor 45, have analog-digital converter AD1～AD4, liquid crystal display 13, RAM42, they are visited by microprocessor 45 by bus 46 separately.In addition, button 11a～11d is connected with microprocessor 45 separately.The ROM of storing software is equipped with in microprocessor 45 inside.In addition, microprocessor 45 can be accepted the instruction that send the outside by the 11a～11d that touches the button.

Be installed in necessary programs in the ROM 47 storage computation processing in the microprocessor 45.That is the function that, has calculating part.The hemoglobin concentration constant storage part 48 of the constant of storage hemoglobin concentration, the hemoglobin saturation with oxygen constant storage part 49 of constant of storage hemoglobin saturation with oxygen also are equipped with in microprocessor 45 inside.Calculation procedure is found out best constant from hemoglobin concentration constant storage part 48 and hemoglobin saturation with oxygen constant storage part 49 and is calculated after the mensuration of finger finishes.In addition, necessary memory block is guaranteed by the RAM 42 that is installed in the device equally in handling calculating.The result of computing is presented at liquid crystal display part.

The necessary programs element is particularly obtained the function that concentration of glucose C uses when having deposited in as processing calculating in ROM.This function definition is as follows.At first, C represents with following formula (8).a _i(i=0,1,2,3) are in advance by a plurality of determination data decisions.Ask a _iStep as follows.

(1) the multiple regression formula of the relation of formation expression normalizing parameter and concentration of glucose C.

(2) obtain the normal equation (simultaneous equations) of simultaneous normalizing parameter by the formula that obtains by method of least square.

(3) obtain coefficient a by normal equation _iThe value of (i=0,1,2,3) is in the substitution multiple regression formula.

At first, make expression concentration of glucose C and normalizing parameter X ₁, X ₂, X ₃The following regression equation (8) of relation.

[several 13]

C＝f(X ₁，X ₂，X ₃)

＝a ₀+a ₁X ₁+a ₂X ₂+a ₃X ₃ ……(8)

Then, in order to make the glucose concentration determination value C with the enzyme electrode method _iThe error minimum find the solution the multiple regression formula, adopt method of least square.Suppose that residual sum of squares (RSS) is D, then D represents with following formula (9).

[several 14]

$D=\underset{i=1}{\overset{n}{\mathrm{\&Sigma;}}}{d_i}^2$

$=\underset{i=1}{\overset{n}{\mathrm{\&Sigma;}}}{(C_i-f({\mathrm{<figure-callout\; id="1"\; label="X\; i"\; filenames="A20041009852300291.png"\; state="\{\{state\}\}">X</figure-callout>}}_i,X_{i2},X_{i3}))}^2$

$=\underset{i=1}{\overset{n}{\mathrm{\&Sigma;}}}{\{C_i-(a_0+a_1{\mathrm{<figure-callout\; id="1"\; label="X\; i"\; filenames="A20041009852300291.png"\; state="\{\{state\}\}">X</figure-callout>}}_i+a_2{X}_{i2}+a_3{X}_{i3})\}}^2\&CenterDot;\&CenterDot;\&CenterDot;\left(9\right)$

Because at a ₀～a ₃To formula (9) when partial differential equals zero, residual sum of squares (RSS) D minimum, thus obtain following formula.

[several 15]

$\frac{\&PartialD;D}{\&PartialD;a_0}=-2\underset{i=1}{\overset{n}{\mathrm{\&Sigma;}}}\{C_i-(a_0+a_1{\mathrm{<figure-callout\; id="1"\; label="X\; i"\; filenames="A20041009852300291.png"\; state="\{\{state\}\}">X</figure-callout>}}_i+a_2{X}_{i2}+a_3{X}_{i3})\}=0$

$\frac{\&PartialD;D}{\&PartialD;a_1}=-2\underset{i=1}{\overset{n}{\mathrm{\&Sigma;}}}{X}_{i1}\{C_i-(a_0+a_1{\mathrm{<figure-callout\; id="1"\; label="X\; i"\; filenames="A20041009852300291.png"\; state="\{\{state\}\}">X</figure-callout>}}_i+a_2{X}_{i2}+a_3{X}_{i3})\}=0$

$\frac{\&PartialD;D}{\&PartialD;a_2}=-2\underset{i=1}{\overset{n}{\mathrm{\&Sigma;}}}{X}_{i2}\{C_i-(a_0+a_1{\mathrm{<figure-callout\; id="1"\; label="X\; i"\; filenames="A20041009852300291.png"\; state="\{\{state\}\}">X</figure-callout>}}_i+a_2{X}_{i2}+a_3{X}_{i3})\}=0$

$\frac{\&PartialD;D}{\&PartialD;a_3}=-2\underset{i=1}{\overset{n}{\mathrm{\&Sigma;}}}{X}_{i3}\{C_i-(a_0+a_1{\mathrm{<figure-callout\; id="1"\; label="X\; i"\; filenames="A20041009852300291.png"\; state="\{\{state\}\}">X</figure-callout>}}_i+a_2{X}_{i2}+a_3{X}_{i3})\}=0...\left(10\right)$

Suppose C, X ₁～X ₃The meansigma methods C that respectively does for oneself _Mean, X _1mean～X _3meanThe time, X _Imean=0 (i=1～3) thus, obtain formula (11) by formula (8).

[several 16]

a ₀＝C _mean-a ₁X _1mean-a ₂X _2mean-a ₃X _3mean

＝C _mean ……(11)

In addition, the change co-variation between the normalizing parameter is with formula (12) expression, normalizing parameter X _iThe co-variation of (i=1～3) and C is with formula (13) expression.

[several 17]

$S_{\mathrm{ij}}=\underset{k=1}{\overset{n}{\mathrm{\&Sigma;}}}(X_{\mathrm{ki}}-X_{\mathrm{imean}})(X_{\mathrm{kj}}-X_{\mathrm{jmean}})=\underset{k=1}{\overset{n}{\mathrm{\&Sigma;}}}{X}_{\mathrm{ki}}{X}_{\mathrm{kj}}(i,j=\mathrm{1,2},3)\&CenterDot;\&CenterDot;\&CenterDot;\left(12\right)$

$S_{\mathrm{iC}}=\underset{k=1}{\overset{n}{\mathrm{\&Sigma;}}}(X_{\mathrm{ki}}-X_{\mathrm{imean}})(C_k-C_{\mathrm{mean}})=\underset{k=1}{\overset{n}{\mathrm{\&Sigma;}}}{X}_{\mathrm{ki}}(C_k-C_{\mathrm{mean}})(i,j=\mathrm{1,2},3)\&CenterDot;\&CenterDot;\&CenterDot;\left(13\right)$

Wushu (11) (12) (13) substitution formula (10) is put in order, obtains simultaneous equations (normal equation) (14), obtains a by separating this equation ₁～a ₃

[several 18]

a ₁S ₁₁+a ₂S ₁₂+a ₃S ₁₃＝S _1C

a ₁S ₂₁+a ₂S ₂₂+a ₃S ₂₃＝S _2C

a ₁S ₃₁+a ₂S ₃₂+a ₃S ₃₃＝S _3C ……(14)

Obtain constant term a with formula (11) ₀The a that more than tries to achieve _i(i=0,1,2,3) are stored among the ROM when manufacturing installation.Do in actual the mensuration at use device, by the normalizing parameter X that obtains by measured value ₁～X ₃In the substitution regression equation (8), calculate concentration of glucose C.

The concrete example of representing concentration of glucose computational process below.By the coefficient of a plurality of data of healthy person and diabetics mensuration being determined regression equation (8), the calculating formula of following concentration of glucose is stored among the microprocessor ROM in advance.

[several 19]

C＝101.7+25.8×X ₁-23.2×X ₂-12.9×X ₃

X ₁～X ₃Be with parameter x ₁～x ₃Parameter after the standardization.Suppose that parameter distributions is a standard profile, 95% value of getting from-2 to+2 of normalizing parameter.

With the measured value of healthy person as an example, normalizing parameter X ₁=-0.06, X ₂=+0.04, X ₃In the above-mentioned formula of=+ 0.10 substitution, obtain C=101mg/dl.In addition, with the measured value of diabetics as an example, normalizing parameter X ₁=+1.35, X ₂=-1.22, X ₃In the above-mentioned formula of=-1.24 substitutions, obtain C=181mg/dl.In addition, hemoglobin concentration is decided to be constant 15g/dl in following formula, and hemoglobin saturation with oxygen is decided to be constant 97%.

Assay method in the past is in the enzyme electrode method, makes the blood and the reagent reacting that obtain by blood sampling, measures the electric weight that is produced by this reaction, measures blood glucose value.Below the measurement result of enzyme electrode method and the measurement result of one embodiment of the present of invention are stated.Measured value with healthy person is an example, when the concentration of glucose of enzyme electrode method is 93mg/dl, measuring the normalizing parameter X that obtains by the inventive method with the moment ₁=-0.06, X ₂=+0.04, X ₃In the above-mentioned formula of=+ 0.10 substitution, obtain C=101mg/dl.In addition, with the measured value of diabetics as an example, when the concentration of glucose of enzyme electrode method is 208mg/dl, with measuring the normalizing parameter X that obtains by the inventive method constantly ₁=+1.35, X ₂=-1.22, X ₃In the above-mentioned formula of=-1.24 substitutions, obtain C=181mg/dl.This result of calculation shows about 13% error, but since usually the device used of blood sugar detection be made into and allow 15～20% error usually, so the precision of this level is considered to enough precision.By above-mentioned result, can obtain concentration of glucose accurately by the inventive method and be confirmed.

Figure 18 is to be that value of calculation, the transverse axis of the concentration of glucose of the inventive method is the measured value of the concentration of glucose of enzyme electrode method with the longitudinal axis, draws the figure that measured value separately forms at a plurality of patients.Can obtain good dependency (correlation coefficient=0.8932) by measuring according to the inventive method.

Claims (16)

1. blood-sugar level measuring device is characterized in that possessing:

Mensuration from a plurality of temperature of body surface, obtain being used to calculating the calorimetry portion of the information of convection heat transfer' heat-transfer by convection amount relevant and radiant heat transfer amount with the heat radiation of above-mentioned body surface,

The oxygen that obtains the information relevant with oxygen amount in the blood measures the bonding part,

Store with above-mentioned a plurality of temperature and above-mentioned blood in the oxygen amount storage part of the relation of corresponding parameters and blood glucose value separately,

To convert above-mentioned parameter separately to by a plurality of measured values that above-mentioned calorimetry portion and above-mentioned oxygen measure the bonding part input and above-mentioned parameter is applicable to the above-mentioned relation that is stored in above-mentioned storage part and calculate blood glucose value calculating part and

The result's that demonstration is calculated by aforementioned calculation portion display part;

Wherein, above-mentioned oxygen measures the bonding part and has the blood flow determination portion that obtains the information relevant with blood flow and obtain the hemoglobin concentration in the blood, the optical detecting portion of hemoglobin saturation with oxygen;

Above-mentioned blood flow determination portion has body surface contact site, first Temperature Detector that is provided with in abutting connection with above-mentioned body surface contact site, connect above-mentioned body surface contact site and the heat-conduction component that is provided with and detect 2nd Temperature Detector of the above-mentioned body surface contact site of above-mentioned heat-conduction component distance more than or equal to the temperature of the position of 3.6mm.

2. blood-sugar level measuring device according to claim 1 is characterized in that above-mentioned heat-conduction component has the length more than or equal to 3.6mm.

3. blood-sugar level measuring device according to claim 1 is characterized in that, above-mentioned heat-conduction component has the pyroconductivity of 0.1J/smK～0.3J/smK scope.

4. blood-sugar level measuring device according to claim 1 is characterized in that above-mentioned heat-conduction component is made of polrvinyl chloride or ABS resin.

5. blood-sugar level measuring device is characterized in that possessing:

Measure the ambient temperature determinator of ambient temperature;

The body surface contact site of contact body surface;

In abutting connection with above-mentioned body surface contact site and be provided with in abutting connection with Temperature Detector;

Mensuration is from the photothermal bolometric detectors of above-mentioned body surface;

The heat-conduction component that connects above-mentioned body surface contact site and be provided with;

In abutting connection with above-mentioned heat-conduction component and be arranged on the above-mentioned body surface contact site of distance more than or equal to the position of 3.6mm, detect the indirect temperature detector of the temperature of the position of leaving above-mentioned body surface contact site;

Shine the light source of the light of at least 2 different wave lengths to above-mentioned body surface contact site;

Detect the catoptrical photodetector that above-mentioned light produces in above-mentioned body surface reflection;

Have with above-mentioned in abutting connection with Temperature Detector, above-mentioned indirect temperature detector, above-mentioned ambient temperature determinator, above-mentioned bolometric detectors and the output separately of above-mentioned photodetector convert to each autoregressive parameter converter section and, store the relation of above-mentioned parameter and blood glucose value in advance and above-mentioned parameter be applicable to that above-mentioned relation calculates the calculating part of the handling part of blood glucose value; With

The display part that shows the result of aforementioned calculation portion output.

6. blood-sugar level measuring device according to claim 5 is characterized in that above-mentioned heat-conduction component has the length more than or equal to 3.6mm.

7. blood-sugar level measuring device according to claim 5 is characterized in that, above-mentioned heat-conduction component has the pyroconductivity of 0.1J/smK～0.3J/smK scope.

8. blood-sugar level measuring device according to claim 5 is characterized in that above-mentioned heat-conduction component is made of polrvinyl chloride or ABS resin.

9. blood-sugar level measuring device is characterized in that having:

The metallic plate that contacts with body surface;

Detect first temperature sensor of the temperature of above-mentioned metallic plate;

The parts that connect above-mentioned metallic plate and be provided with;

The above-mentioned metallic plate of above-mentioned member distance more than or equal to the position adjacency of 3.6mm second temperature sensor;

Mensuration is from the photothermal thermal detector of above-mentioned body surface;

Light source to above-mentioned metallic plate irradiates light;

The photodetector of the light behind the above-mentioned body surface of detection irradiation; With

The calculating part of blood glucose value is calculated in output separately based on above-mentioned first temperature sensor, above-mentioned second temperature sensor, above-mentioned thermal detector and above-mentioned photodetector.

10. blood-sugar level measuring device according to claim 9 is characterized in that above-mentioned parts have the length more than or equal to 3.6mm.

11. blood-sugar level measuring device according to claim 9 is characterized in that, above-mentioned parts have the pyroconductivity of 0.1J/smK～0.3J/smK scope.

12. blood-sugar level measuring device according to claim 9 is characterized in that, above-mentioned parts are made of polrvinyl chloride or ABS resin.

13. a blood-sugar level measuring device is characterized in that possessing:

Measure the ambient temperature determinator of ambient temperature;

The body surface contact site of contact body surface;

In abutting connection with above-mentioned body surface contact site and be provided with in abutting connection with Temperature Detector;

Mensuration is from the photothermal bolometric detectors of above-mentioned body surface;

The heat-conduction component that connects above-mentioned body surface contact site and be provided with;

In abutting connection with above-mentioned heat-conduction component and be arranged on the above-mentioned body surface contact site of distance more than or equal to the position of 3.6mm, detect the indirect temperature detector of the temperature of the position of leaving above-mentioned body surface contact site;

The storage part of the information that storage is relevant with hemoglobin saturation with oxygen with the hemoglobin concentration in the blood;

Have with above-mentioned output in abutting connection with Temperature Detector, above-mentioned indirect temperature detector, above-mentioned ambient temperature determinator and above-mentioned bolometric detectors convert to a plurality of parameters converter section and, store the relation of above-mentioned parameter and blood glucose value in advance and above-mentioned parameter be applicable to that above-mentioned relation calculates the calculating part of the handling part of blood glucose value; With

Demonstration is by the result's of aforementioned calculation portion output display part.

14. blood-sugar level measuring device according to claim 13 is characterized in that, above-mentioned heat-conduction component has the length more than or equal to 3.6mm.

15. blood-sugar level measuring device according to claim 13 is characterized in that, above-mentioned heat-conduction component has the pyroconductivity of 0.1J/smK～0.3J/smK scope.

16. blood-sugar level measuring device according to claim 13 is characterized in that, above-mentioned heat-conduction component is made of polrvinyl chloride or ABS resin.

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